RESUMEN
Nanocarriers can deliver drugs to specific organs or cells, potentially bridging the gap between a drug's function and its interaction with biological systems such as human physiology. The untapped potential of nanotechnology stems from its ability to manipulate materials, allowing control over physical and chemical properties and overcoming drug-related problems, e.g., poor solubility or poor bioavailability. For example, most protein drugs are administered parenterally, each with challenges and peculiarities. Some problems faced by bioengineered macromolecule drugs leading to poor bioavailability are short biological half-life, large size and high molecular weight, low permeability through biological membranes, and structural instability. Nanotechnology emerges as a promising strategy to overcome these problems. Nevertheless, the delivery system should be carefully chosen considering loading efficiency, physicochemical properties, production conditions, toxicity, and regulations. Moving from the bench to the bedside is still one of the major bottlenecks in nanomedicine, and toxicological issues are the greatest challenges to overcome. This review provides an overview of biotech drug delivery approaches, associated nanotechnology novelty, toxicological issues, and regulations.
Asunto(s)
Nanopartículas , Nanotecnología , Humanos , Sistemas de Liberación de Medicamentos , Nanomedicina , Preparaciones Farmacéuticas/química , Proteínas , Sustancias Macromoleculares , Nanopartículas/químicaRESUMEN
Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-ß-CD), as shown by the phase solubility study. The resulting complex (HP-ß-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and 1H-NMR. The freeze-dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2% mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug delivery.
Asunto(s)
2-Hidroxipropil-beta-Ciclodextrina/química , Anestesia Local/métodos , Anestésicos Locales/uso terapéutico , Capsaicina/uso terapéutico , Composición de Medicamentos/métodos , Excipientes/química , Hiperalgesia/tratamiento farmacológico , Mepivacaína/uso terapéutico , Dolor/tratamiento farmacológico , Animales , Rastreo Diferencial de Calorimetría , Capsaicina/química , Carragenina/efectos adversos , Modelos Animales de Enfermedad , Estabilidad de Medicamentos , Quimioterapia Combinada , Hiperalgesia/inducido químicamente , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Microscopía Electrónica de Rastreo , Manejo del Dolor/métodos , Solubilidad , Difracción de Rayos XRESUMEN
Oral route maintains its predominance among the ones used for drug delivery, especially when medicines are self-administered. If the dosage form is solid, therapy gains in dose precision and drug stability. Yet, some active pharmaceutical substances do not present the required solubility, permeability, or release profile for incorporation into traditional matrices. The combination of nanostructured drugs (nanoparticle [NP]) with these matrices is a new and little-explored alternative, which could bring several benefits. Therefore, this review focused on combined delivery systems based on nanostructures to administer drugs by the oral cavity, intended for buccal, sublingual, gastric, or intestinal absorption. We analyzed published NP-in-matrix systems and compared main formulation characteristics, pharmacokinetics, release profiles, and physicochemical stability improvements. The reported formulations are mainly semisolid or solid polymers, with polymeric or lipid NPs and one active pharmaceutical ingredient. Regarding drug specifics, most of them are poorly permeable or greatly metabolized. The few studies with pharmacokinetics showed increased drug bioavailability and, sometimes, a controlled release rate. From our knowledge, the gathered data make up the first focused review of these trendy systems, which we believe will help to gain scientific deepness and future advancements in the field.
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Excipient interaction has become essential knowledge for rational formulation design of nanoparticles. Nanostructured lipid carriers (NLCs) include at least three types of excipient, which enhance excipient interaction possibilities and relevance. The present article introduces an alternative approach for evaluating a great number of excipients with few samples, using NLC as a model delivery system. This approach is based on two sequential experiments using Hall-2 experimental design and analysis of excipient interactions in respect to their physicochemical properties by multilevel statistics. NLCs were prepared using a hot emulsification-ultrasonication method with lidocaine and nine excipients (solid lipids, oils and surfactants). The evaluated parameters were z-average size (DLS), dispersity (DLS), zeta potential (electrophoretic mobility) and entrapment efficiency (HPLC). Cetyl palmitate, beeswax, castor oil, capric/caprylic acid and polysorbate 80 all presented larger effects amongst the studied factors as well as a clear pattern of synergistic interactions. Following the verified trends, we produced an optimized NLC that exhibited all desirable physicochemical characteristics and a modified drug release profile. Our results demonstrate the methodology's robustness, which can be applied to other nanoparticles and establish a cost-effective excipient evaluation.
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A great number of patients have difficulty swallowing or needle fear. Therefore, buccal and orodispersible dosage forms (ODFs) represent an important strategy to enhance patient compliance. Besides not requiring water intake, swallowing or needles, these dosage forms allow drug release modulation. ODFs include oral lyophilizates or wafers, which present even faster disintegration than its compressed counterparts. Lyophilization can also produce buccal wafers that adhere to mucosa for sustained drug release. Due to the subject relevance and recent research growth, this review focused on oral lyophilizate production technology, formulation features, and therapy gains. It includes Critical Quality Attributes (CQA) and Critical Process Parameters (CPP) and discusses commercial and experimental examples. In sum, the available commercial products promote immediate drug release mainly based on biopolymeric matrixes and two production technologies. Therapy gains include substitution of traditional treatments depending on parenteral administration and patient preference over classical therapies. Experimental wafers show promising advantages as controlled release and drug enhanced stability. All compiled findings encourage the development of new wafers for several diseases and drug molecules.
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Use of nanoscale devices as carriers for drugs and imaging agents has been extensively investigated and successful examples can already be found in therapy. In parallel, recombinant DNA technology together with molecular biology has opened up numerous possibilities for the large-scale production of many proteins of pharmaceutical interest, reflecting in the exponentially growing number of drugs of biotechnological origin. When we consider protein drugs, however, there are specific criteria to take into account to select adequate nanostructured systems as drug carriers. In this review, we highlight the main features, advantages, drawbacks and recent developments of nanostructures for protein encapsulation, such as nanoemulsions, liposomes, polymersomes, single-protein nanocapsules and hydrogel nanoparticles. We also discuss the importance of nanoparticle stabilization, as well as future opportunities and challenges in nanostructures for protein drug delivery.